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Meta-Analysis
. 2021 Feb 9;16(2):e0246480.
doi: 10.1371/journal.pone.0246480. eCollection 2021.

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials

Joseph E Blais  1 , Gloria Kin Yi Tong  2 , Swathi Pathadka  1 , Michael Mok  3 , Ian C K Wong  1   4 , Esther W Chan  1
Affiliations
Meta-Analysis

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials

Joseph E Blais et al. PLoS One. .

Abstract

Objective: To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.

Methods: Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.

Results: We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).

Conclusions: The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

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Conflict of interest statement

The authors have read the journal’s policy and have the following competing interests: EWC has received honorarium from the Hospital Authority, research grants from Research Grants Council (RGC, HKSAR), Research Fund Secretariat of the Food and Health Bureau (HMRF, HKSAR), National Natural Science Fund of China, National Health and Medical research Council NHMRC, Australia), Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. ICKW has received research grants from Research Grants Council (RGC, Hong Kong), Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, Bayer, Amgen, and grants from European Union FP7 program, outside the submitted work. GKYT is an employee of Pfizer Upjohn Hong Kong Limited. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. The other authors have no competing interests to declare.

Figures

Fig 1
Fig 1. PRISMA (preferred reporting items for systematic reviews and meta-analyses) flowchart of head-to-head studies evaluating statin and fibrate monotherapy on mortality and cardiovascular outcomes.
Fig 2
Fig 2. Forest plot of comparison: Statins versus fibrates, outcome: Cardiovascular mortality.
Fig 3
Fig 3. Forest plot of comparison: Statins versus fibrates, outcome: All-cause mortality.
Fig 4
Fig 4. Forest plot of comparison: Statins versus fibrates, outcome: Major cardiovascular events.
Fig 5
Fig 5. Forest plot of comparison: Statins versus fibrates, outcome: Myocardial infarction.
Fig 6
Fig 6. Forest plot of comparison: Statins versus fibrates, outcome: Coronary artery disease.
Fig 7
Fig 7. Forest plot of comparison: Statins versus fibrates, outcome: Unstable angina.
Fig 8
Fig 8. Forest plot of comparison: Statins versus fibrates, outcome: Stroke.
Fig 9
Fig 9. Forest plot of comparison: Statins versus fibrates, outcome: Study withdrawal due to adverse effects.
Fig 10
Fig 10. Forest plot of comparison: Statins versus fibrates, outcome: Serious adverse effects.
Fig 11
Fig 11. Forest plot of comparison: Statins versus fibrates, outcome: Myalgia.
Fig 12
Fig 12. Forest plot of comparison: Statins versus fibrates, outcome: Elevated alanine aminotransferase.
Fig 13
Fig 13. Forest plot of comparison: Statins versus fibrates, outcome: Elevated serum creatinine.
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The author(s) received no specific funding for this work. JEB is supported by the Hong Kong Research Grants Council as a recipient of the Hong Kong PhD Fellowship Scheme. When this study began, GKYT was both a student at the University of Hong Kong and an employee at Otsuka Pharmaceutical (H.K.) Limited. She is currently employed by Pfizer Upjohn Hong Kong Limited. The funders provided support in the form of salaries for GKYT and JEB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.